M-CSF is a secreted cytokine which influences hematopoietic stem cells to differentiate into macrophages or other related cell types. The active form of M-CSF is found extracellularly as a disulfide-linked homodimer. Three different isoforms of M-CSF are found extracellularly: secreted glycosylated M-CSF, secreted proteoglycan M-CSF, and cell-surface M-CSF.
M-CSF is a validated target for therapeutic invention, in particularly for the treatment of inflammatory disorders, such as e.g. rheumatoid arthritis. See e.g. U.S. Pat. No. 8,142,777 which is incorporated by reference. Several molecules are under development which target M-CSF, including antibody approaches. See e.g. WO2005/030124 (Warner-Lambert/Pfizer) WO2005/068503 and (Chiron/Novartis).
The present disclosure provides novel antibodies and antibody fragments which are superior to the anti-M-CSF antibodies known from the prior art. In particular, the antibodies and antibody fragments of the present disclosure specifically bind to M-CSF and inhibit the binding of M-CSF to the M-CSF receptor with an IC50 of 10 pM or less in a receptor binding inhibition assay comprising M-CSF at a final concentration of 12.5 pM. In addition, the antibodies exhibit functional properties which are highly desirable for clinical development and which never have been observed before.